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Exploring the biological contributions to human health: Does sex matter? The Institute of Medicine answers "yes."
... Anthropometric parameters such as bodyweight, fat distribution and differences in pharmacokinetics and pharmacodynamics means that women are more sensitive to some drugs, have altered clearance kinetics and may experience more drug interactions [67]. In humans, oestrogen and progesterone are endogenous to both sexes, but differ in their circulating levels [68,69]. Unlike progesterone, there are many forms of oestrogen: estrone (E1), estradiol (E2), estriol (E3) and other minor oestrogens, but the major oestrogen is E2. ...
... Oestrogens are discussed more often than progesterones in relation to senescence, but in this study levonorgestrel, a progesterone, had a larger effect on senescence than the oestrogens. Diethylstilboestrol decreased proliferation in male cells, which is at odds with oestrogen's often growth-inducing effects, e.g. during the female pubertal growth spurt [68]. At the present time, it is not clear whether the observed sex differences arise from differences in bioavailability, or from an undescribed noncanonical role of the hormones over and above canonical oestrogen/progesterone signalling, particularly given the senomorphic effect occurs with treatment of either a synthetic oestrogen or a progesterone. ...
Repurposing previously approved drugs may fast track the route to clinic for potential senotherapeutics and improves the inefficiency of the clinical drug development pipeline. We carried out a repurposing screen of 240 clinically approved molecules in human primary dermal fibroblasts for effects on CDKN2A expression. Molecules demonstrating effects on CDKN2A expression underwent secondary screening for senescence-associated beta galactosidase (SAB) activity, based on effect size, direction and/or molecule identity. Selected molecules then underwent a more detailed assessment of senescence phenotypes including proliferation, apoptosis, DNA damage, senescence-associated secretory phenotype (SASP) expression and regulators of alternative splicing. A selection of the molecules demonstrating effects on senescence were then used in a new bioinformatic structure-function screen to identify common structural motifs. 90 molecules displayed altered CDKN2A expression at one or other dose, of which 15 also displayed effects on SAB positivity in primary human dermal fibroblasts. Of these, three were associated with increased SAB activity, and 11 with reduced activity. The female synthetic sex hormones; diethylstilboestrol, ethynyl estradiol and levonorgestrel; were all associated with a reduction in aspects of the senescence phenotype in male cells, with no effects visible in female cells. Finally, we identified that the 30 compounds that decreased CDKN2A activity the most had a common substructure linked to this function. Our results suggest that several drugs licenced for other indications may warrant exploration as future senotherapies, but that different donors and potentially different sexes may respond differently to senotherapeutic compounds. This underlines the importance of consideration of donor-related characteristics when designing drug screening platforms.
... However, because the number of total participants in studies grew over the 30 years, the total number of participants with an unknown gender (not declared in the article) increased by over $300%. Given the awareness of sex as a biological factor (3,38), it is surprising that several studies in 2021 did not report participant sex or gender, and these studies were approved by reviewers and editors for publication. The reporting of sex and gender remains an area of growth even in top-tiered journals (39). ...
... The increase of women participants over the 30 years coincides with mandates from governing and funding agencies of biomedical research in the United States and across the world. Sex and gender, however, are important biological variables and significant determining factors in exercise responses and health outcomes (3,12,38,40). In 2015, the National Institutes of Health (NIH) released a mandate [Consideration of Sex as a Biological Variable in NIH-Funded Research (NOT-OD-15-102)] that sex and gender must be considered in all research studies (https://grants.nih.gov/grants/guide/notice-files/ ...
Historically, low representation of women participants in exercise science and physiology studies has led to a lack of understanding in the response of women to exercise and therapeutic interventions. We hypothesized (1) the number of women authors, participants and editorial board members increased over 30 years (1991-2021) and (2) larger representation of women as editors and authors is associated with more women participants. Gender (man/woman) of editorial board members (n=394), and authors (n=5,735) and participants (n=2,984,883) of 972 original research articles with human participants published in 1991 and 2021, were analyzed from three journals: Journal of Applied Physiology, Medicine and Science in Sports and Exercise, and British Journal of Sports Medicine. Between 1991 to 2021, the average percent women per article as participants (21.9±31.7% vs 36.3±30.3% respectively, P<0.001), authors (16.4±22.4% vs 30.9±24.0%, P<0.001), and as editorial board members (13.3±5.4% vs 41.5±7.3%, P=0.006) increased. In 2021, the gender proportion of participants in large data sets were similar (50.2±20.2% women). However, studies with smaller data sets (i.e., <~3,000 participants) included less women (35.6±30.6%). Women participants (%) were less when the last author was a man rather than a woman in 1991 (19.9±29.5% vs 34.3±42.2%) and 2021 (31.6±27.7% vs 51.7±33.4%). In 2021, there was a positive correlation between author and participant gender (% women) (r=0.42, P<0.001). Our data suggest the low representation of women in exercise science and physiology research could be resolved with equitable numbers of women authors and editors and by encouraging men authors to study both women and men participants.
... In a similar vein, sex and gender differences have been a focus of interest in alpha-synucleinopathies in recent years, due to their potential to disentangle sex-specific disease phenotypes, and translate them to develop novel sex-specific therapeutics -known as a 'benchto-bedside' approach (6)(7)(8). According to the Institute of Medicine's Committee on Sex and Gender Differences, sex and gender differences are biological, physiological, and clinical differences between males and females that arise due to environmental factors and biological effects due to sex chromosomes and gonadal hormones (9). ...
... As for systematic reviews and meta-analyzes, the AMSTAR-2 is a comprehensive critical appraisal tool focusing on weaknesses in multiple domains. AMSTAR-2 assesses 16 questions, among which 7 are critical domains (21) (Questions 2,4,7,9,11,13,and 15; See Supplementary section). Subsequent evaluation is conceptualized into three options, "Yes, " "Partial Yes, " and "No. ...
Background
Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective properties of female sex hormones (especially estrogen). The potential pathomechanisms of any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook to systematically review, and to critically assess, contemporary evidence on sex and gender differences in alpha-synucleinopathies using a bench-to-bedside approach.
Methods
In this systematic review, studies investigating sex and gender differences in alpha-synucleinopathies (Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson’s Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) from 2012 to 2022 were identified using electronic database searches of PubMed, Embase and Ovid.
Results
One hundred sixty-two studies were included; 5 RBD, 6 MSA, 20 DLB and 131 PD studies. Overall, there is conclusive evidence to suggest sex-and gender-specific manifestation in demographics, biomarkers, genetics, clinical features, interventions, and quality of life in alpha-synucleinopathies. Only limited data exists on the effects of distinct sex hormones, with majority of studies concentrating on estrogen and its speculated neuroprotective effects.
Conclusion
Future studies disentangling the underlying sex-specific mechanisms of alpha-synucleinopathies are urgently needed in order to enable novel sex-specific therapeutics.
... In 2013 we reviewed the topic of sex differences in myocarditis and DCM (3). At that time the National Institutes of Health (NIH) had not updated its guidance for the inclusion of sex as a biological variable (SABV) in study design, data analysis and reporting of findings for NIH supported studies (4)(5)(6), and few studies in the literature focused on the topic. In that review, we called for greater translational research efforts in understanding the pathogenesis of sex differences in myocarditis and expressed the need to develop multicenter biobanks that could link specific phenotypes of samples with a special focus on including both sexes (3). ...
... First, sex and gender are not interchangeable terms. Sex refers to biological differences attributed to chromosomes, hormones, reproductive anatomy, gene expression, etc., and typically refers to a binary of male or female but can include intersex (5,8,9). Gender, on the other hand, is a social construct that is rooted in biology but affected by environment and experience. ...
Myocarditis is frequently caused by viral infections, but animal models that closely resemble human disease suggest that virus-triggered autoimmune disease is the most likely cause of myocarditis. Myocarditis is a rare condition that occurs primarily in men under age 50. The incidence of myocarditis rose at least 15x during the coronavirus disease 2019 (COVID-19) pandemic from 1–10 to 150–400 cases/100 000 individuals, with most cases occurring in men under age 50. COVID-19 vaccination was also associated with rare cases of myocarditis primarily in young men under 50 years of age with an incidence as high as 50 cases/100 000 individuals reported for some mRNA vaccines. Sex differences in the immune response to COVID-19 are virtually identical to the mechanisms known to drive sex differences in myocarditis pre-COVID based on clinical studies and animal models. The many similarities between COVID-19 vaccine-associated myocarditis to COVID-19 myocarditis and non-COVID myocarditis suggest common immune mechanisms drive disease.
... It is no longer acceptable for basic science studies to be performed exclusively in male animals, or for women to be excluded from clinical trials. Sex differences in genetics, epigenetics (Novella et al., 2021), molecular biology (Wizemann and Pardue, 2001), immunology (Klein and Flanagan, 2016), drug metabolism (Soldin and Mattison, 2009), and anatomy (Dominelli et al., 2018;Ripoll et al., 2020;St. Pierre et al., 2022) exist. ...
... The male genome differs from the female genome in the number of X chromosomes that it contains, as well as by the presence of a Y chromosome. A change in the activity of just a single gene can have a large effect on the organism that carries that gene, meaning that any sex differenceseven one genecan impact on physiology (Wizemann and Pardue, 2001). Sex differences in gene expression and co-expression have been studied using RNA-sequencing in different tissue types (Hartman et al., 2021;Khodursky et al., 2022). ...
Personalised medicine and the development of a virtual human or a digital twin comprises visions of the future of medicine. To realise these innovations, an understanding of the biology and physiology of all people are required if we wish to apply these technologies at a population level. Sex differences in health and biology is one aspect that has frequently been overlooked, with young white males being seen as the “average” human being. This has not been helped by the lack of inclusion of female cells and animals in biomedical research and preclinical studies or the historic exclusion, and still low in proportion, of women in clinical trials. However, there are many known differences in health between the sexes across all scales of biology which can manifest in differences in susceptibility to diseases, symptoms in a given disease, and outcomes to a given treatment. Neglecting these important differences in the development of any health technologies could lead to adverse outcomes for both males and females. Here we highlight just some of the sex differences in the cardio-respiratory systems with the goal of raising awareness that these differences exist. We discuss modelling studies that have considered sex differences and touch on how and when to create sex-specific models. Scientific studies should ensure sex differences are included right from the study planning phase and results reported using sex as a biological variable. Computational models must have sex-specific versions to ensure a movement towards personalised medicine is realised.
... Evolutionarily conserved sex differences exist in both innate and adaptive immune responses 1,2 . While males are less susceptible to autoimmunity, they also mount a less potent antiviral immune response than females 3 . For instance, males have a higher human cytomegalovirus (HCMV) burden after infection, suggesting increased susceptibility to viral threats 4 . ...
... Sex is a critical biological variable in determining outcomes to viral infections 3 . This was recently illustrated with COVID-19, in which male sex was identified as a major risk factor for severe disease 5 . ...
Viral infection outcomes are sex biased, with males generally more susceptible than females. Paradoxically, the numbers of antiviral natural killer (NK) cells are increased in males. We demonstrate that while numbers of NK cells are increased in male mice, they display decreased effector function compared to females in mice and humans. These differences were not solely dependent on gonadal hormones, because they persisted in gonadectomized mice. Kdm6a (which encodes the protein UTX), an epigenetic regulator that escapes X inactivation, was lower in male NK cells, while NK cell-intrinsic UTX deficiency in female mice increased NK cell numbers and reduced effector responses. Furthermore, mice with NK cell-intrinsic UTX deficiency showed increased lethality to mouse cytomegalovirus. Integrative multi-omics analysis revealed a critical role for UTX in regulating chromatin accessibility and gene expression critical for NK cell homeostasis and effector function. Collectively, these data implicate UTX as a critical molecular determinant of sex differences in NK cells.
... In 2013 we reviewed the topic of sex differences in myocarditis and DCM (3). At that time the National Institutes of Health (NIH) had not updated its guidance for the inclusion of sex as a biological variable (SABV) in study design, data analysis and reporting of findings for NIH supported studies (4)(5)(6), and few studies in the literature focused on the topic. In that review, we called for greater translational research efforts in understanding the pathogenesis of sex differences in myocarditis and expressed the need to develop multicenter biobanks that could link specific phenotypes of samples with a special focus on including both sexes (3). ...
... First, sex and gender are not interchangeable terms. Sex refers to biological differences attributed to chromosomes, hormones, reproductive anatomy, gene expression, etc., and typically refers to a binary of male or female but can include intersex (5,8,9). Gender, on the other hand, is a social construct that is rooted in biology but affected by environment and experience. ...
In the past decade there has been a growing interest in understanding sex and gender differences in myocarditis and dilated cardiomyopathy (DCM), and the purpose of this review is to provide an update on this topic including epidemiology, pathogenesis and clinical presentation, diagnosis and management. Recently, many clinical studies have been conducted examining sex differences in myocarditis. Studies consistently report that myocarditis occurs more often in men than women with a sex ratio ranging from 1:2–4 female to male. Studies reveal that DCM also has a sex ratio of around 1:3 women to men and this is also true for familial/genetic forms of DCM. Animal models have demonstrated that DCM develops after myocarditis in susceptible mouse strains and evidence exists for this progress clinically as well. A consistent finding is that myocarditis occurs primarily in men under 50 years of age, but in women after age 50 or post-menopause. In contrast, DCM typically occurs after age 50, although the age that post-myocarditis DCM occurs has not been investigated. In a small study, more men with myocarditis presented with symptoms of chest pain while women presented with dyspnea. Men with myocarditis have been found to have higher levels of heart failure biomarkers soluble ST2, creatine kinase, myoglobin and T helper 17-associated cytokines while women develop a better regulatory immune response. Studies of the pathogenesis of disease have found that Toll-like receptor (TLR)2 and TLR4 signaling pathways play a central role in increasing inflammation during myocarditis and in promoting remodeling and fibrosis that leads to DCM, and all of these pathways are elevated in males. Management of myocarditis follows heart failure guidelines and there are currently no disease-specific therapies. Research on standard heart failure medications reveal important sex differences. Overall, many advances in our understanding of the effect of biologic sex on myocarditis and DCM have occurred over the past decade, but many gaps in our understanding remain. A better understanding of sex and gender effects are needed to develop disease-targeted and individualized medicine approaches in the future.
... HIV pre-exposure prophylaxis (PrEP) reduces HIV transmission to women and is partner-and event-independent [17][18][19], which is empowering for WICL who may rely on partners for basic subsistence and have limited social capital to negotiate male partners' condom use [20][21][22]. Despite demonstrated efficacy in clinical trials, PrEP use in the U.S. remains low overall and especially low in women. ...
Background
Women involved in the criminal legal system have elevated rates of opioid use disorder, which is treatable, and HIV, which is preventable with pre-exposure prophylaxis (PrEP). There are significant social and structural barriers to integrated delivery of PrEP and medications for opioid use disorder (MOUD), limiting women’s ability to access these life-saving interventions. In a two parallel-arm randomized controlled trial, we are assessing an innovative eHealth delivery model that integrates PrEP with MOUD and is tailored to meet the specific needs of women involved in the criminal legal system.
Methods
We will recruit and enroll 250 women involved in the criminal legal system with opioid use disorder across two diverse settings (New Haven, CT and Birmingham, AL). Participants will be randomized to (a) the “Athena strategy,” which includes a PrEP decision aid and integrated PrEP/MOUD delivery via eHealth; or (b) enhanced standard of care (SOC) that includes a decision aid-only. During 6-month follow-up, we will assess PrEP initiation as the primary clinical outcome and implementation outcomes that include acceptability, adoption, feasibility, fidelity, implementation cost, and sustainability.
Discussion
Results could help determine if reducing the social and structural barriers to PrEP and MOUD for women involved in the criminal legal system will facilitate engagement in treatment and prevention services, thus alleviating health disparities.
Trial registration
Clinicaltrials.gov (NCT05547048). Registered September 15, 2022. https://clinicaltrials.gov/study/NCT05547048?term=NCT05547048&rank=1 .
... Available evidence confirms that life expectancy differs at all ages, with females living longer than males [1,2]. However, the sex gap in life expectancy converges with age [3]. ...
The female advantage in life expectancy sits uneasily with female disadvantage in health and well-being in later life compared to their male counterparts. This health disparity has been suggested to rest on sex difference in allostatic load (AL). We aim to delineate the sex-specific age trajectories of AL among midlife and older adults in China and to interpret the contradiction between the female advantage in life expectancy and their disadvantage in health in later life from the perspective of physiological dysregulation. Using data from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011 and 2015, we included 3,836 male and 3,308 female Chinese adults aged 45 and older. Two-level mixed-effects models were fitted to examine how AL changed over time. Missing values were addressed by performing multiple imputations using chained equations. Results show AL increases with age for both sexes, with a steeper rise in females and a slight decline in males after adjusting for the sex-age interaction. Older males born before the People’s Republic of China (PRC) exhibited different AL trajectories from younger cohorts. The sex-specific trajectories converge around the late 60s, with females surpassing males, aligning with the life expectancy-health paradox. The presence of a healthier older male cohort in CHARLS suggests future studies should account for cohort effects.
... The enrolment and participation of fewer women in RCTs, as an illustrative example, renders sex-based differences in disease aetiology, epidemiology, pathogenesis, and treatment effects to remain hidden or undiscovered [16][17][18] . Women who are pregnant or lactating are also frequently excluded from medical RCT participation due to prohibitive regulatory barriers 19,20 . ...
Background
Equality, diversity and inclusion (EDI) has gained discursive momentum across multiple arenas, including in maternal health research. As a preliminary exploration for future discussion and development, we undertook a scoping review to identify the types, frequency, and extent of EDI characteristics that were measured and reported in randomised controlled trials (RCTs) of intrapartum interventions specifically.
Methods
Joanna Briggs Institute methodological guidance for scoping reviews guided the conduct of the review. The population were women of any parity and risk category who were enrolled in intrapartum RCTs in any birth setting or geographical location. The concept was measured and reported EDI characteristics. CINAHL, MEDLINE, PsycINFO, EMBASE, and CENTRAL were searched from January 2019 to March 2024. Data were extracted using a pre-designed form. The findings were summarised and narratively reported supported by illustrative tables and graphs.
Results
Two-hundred and forty-seven RCTs from 49 countries were included. Eleven EDI characteristics were measured or reported in at least one RCT, although frequency varied. Religion, for example, featured in three RCTs only, whereas Age featured in 222 RCTs. How the EDI characteristics featured also varied. Race/Ethnicity, for example, was described in 21 different ways in 25 RCTs. Similarly, Education was reported in 62 different ways across 96 RCTs. Ninety RCTs limited inclusion to nulliparous participants only, six RCTs required participants to have a minimum educational level, 127 RCTs had inclusion age cut-offs although 23 different variations of this were noted and 15 RCTs excluded participants on the grounds of disability.
Conclusions
This scoping review highlights EDI characteristic measurement and reporting deficits in intrapartum RCTs. There is a critical need for improvements in designing, conducting, and reporting RCTs to incorporate EDI. By adopting more extensive EDI practices a greater understanding of healthcare treatments and innovations leading to enhanced maternal health equity could be achieved.
... In differentiating sex and gender, sex is a term used to refer to the biological and physiological differences between men and women, while gender is used to refer to the societal roles and expectations of men and women (Habib et al., 2020;Wizemann & Pardue, 2001). This approach "improves the understanding that the sexual division of labour, biological differences, employment patterns, social roles and social structures all contribute to gender-specific patterns of occupational hazards and risks" (ILO, 2013). ...
Background
The number of women in the chemical industry has recently increased due to more women pursuing science careers. It is necessary, therefore, to analyze the emerging health risks for female workers in the chemical industry. This study examines the relationship between occupational health and sex/gender in the chemical industry, with a gender perspective.
Methods
We present a scoping review ( n = 97). After removing duplicates and applying eligibility criteria, we selected 27 articles published in the last decade that explored the industry’s occupational risks.
Findings
Most of the papers include predominantly male samples and describe adult populations, mainly from developed countries. The studies focus on various employment contexts of chemical industries. We identified health risks in oncology, dermatology, and the respiratory system, among others. We found that particular emphasis was given to the relationship between occupational exposure and cancer, especially breast cancer. Furthermore, we observed sex/gender differences in the prevalence of respiratory and dermatological disorders. These results highlight the need to consider specific sex/gender-based health risk factors in the chemical industry.
Conclusions/Application to Practice
The chemical industry is considered a crucial health determinant, however, the studies focused on sex/gender-based differences without considering gender-specific physiology and work circumstances. Although some studies do mention sex/gender disparities, such as occupational rhinitis, which is more frequent in women, studies are scarce. The absence of a segregated analysis with a gender perspective could lead to the ignorance of emerging health risks for female workers, highlighting the urgent need to include a gender perspective in future research.
... Sex in this context refers to a child's biological sex assigned at birth, typically treated as binary, i.e., either assigned male or assigned female (Polderman et al., 2018). Assignment as male or female is usually based on reproductive organs and functions (e.g., Wizemann & Pardue, 2001). In contrast to sex, gender refers to a person's gender identity, i.e., a person's self-presentation as, for example, female, male, or an alternative self-assignment (e.g., genderqueer). ...
Objective: This paper examines to what extent genetic and environmental influences contribute to differences in family leisure activities of girls and boys. Background: While family leisure activities have been described as relevant for child development, it remains unclear what accounts for differences in the leisure behavior of girls and boys. While research emphasized the importance of the environment, e.g., in relation to gender role socialization, other studies pointed to biological and, thus, genetic differences as explanatory factors. Method: The analysis is based on 954 female and 1036 male twins aged 10-12 years who are part of the first wave of the German Twin Family Panel Study. Our analysis examines five family leisure activities using variance decompositions and gene-environment interaction models. Results: Overall, there were only minor differences between girls and boys in the contributions of genes and environments to family leisure activities. Only for singing and making music did influences from the environment common to both twins contribute more strongly to the performance of these activities in the girls than in the boys. Conclusion: There is no evidence that genetic differences lead to differences in family leisure behavior between girls and boys in the activities considered here. Existing differences are more likely to be due to environmental influences.
... Nevertheless, a paradigm shift is underway, acknowledging the significance of comprehensively considering sex differences in research settings. Initiatives such as the Committee on Understanding the Biology of Sex and Gender Differences, formed by the Institute of Medicine, USA, in 1999, advocates for expanding the "research on sex at a cellular level" from birth to death and across species in an attempt to eliminate "barriers to advancement of science in health and illness" [12]. Moreover, emerging evidence underscores the existence of sex differences in kidney function and disease, highlighting the imperative to incorporate sex as a significant variable in research [13]. ...
In vitro models serve as indispensable tools for advancing our understanding of biological processes, elucidating disease mechanisms, and establishing screening platforms for drug discovery. Kidneys play an instrumental role in the transport and elimination of drugs and toxins. Nevertheless, despite the well-documented inter-individual variability in kidney function and the multifaceted nature of renal diseases—spanning from their origin, trigger and which segment of the kidney is affected—to presentation, progression and prognosis, few studies take into consideration the variable of sex. Notably, the inherent disparities between female and male biology warrants a more comprehensive representation within in vitro models of the kidney. The omission of sex as a fundamental biological variable carries the substantial risk of overlooking sex-specific mechanisms implicated in health and disease, along with potential differences in drug responsiveness and toxicity profiles between sexes. This review emphasizes the importance of incorporating cellular, biological and functional sex-specific features of renal activity in health and disease in in vitro models. For that, we thoroughly document renal sex-specific features and propose a strategic experimental framework to integrate sex-based differences into human kidney in vitro models by outlining critical design criteria to elucidate sex-based features at cellular and tissue levels. The goal is to enhance the accuracy of models to unravel renal mechanisms, and improve our understanding of their impact on drug efficacy and safety profiles, paving the way for a more comprehensive understanding of patient-specific treatment modalities.
... Women face unique health challenges over the course of their lives, due to a combination of biological sex differences and sociocultural influences related to gender [1]. Disparities exist and have been documented for women across disease states and life stages that touch every race, ethnic group, geographic location, and socioeconomic status. ...
Women comprise approximately half of the world’s population, yet they are often underrepresented and inadequately considered in medical and public health research and in health care delivery in the United States and around the world. Elucidating sex and gender differences in disease and fundamental hormonal drivers of women’s health is instrumental to informing our overall understanding of human health and improving women’s health outcomes across the lifespan. The Society for Women’s Health Research and ECH Alliance–The Global Health Connector hosted a women’s health program as part of the United Nations 79th General Assembly Science Summit. Here, I briefly describe the basis for this convening to address global gender health gaps and reflect on the event’s presentations and discussions to recognize and better integrate women’s unique health needs in the sustainable development goals.
... In Forschung, medizinischer Lehre und klinischer Praxis wurde beginnend in den USA und Kanada vor gut 30 Jahren mit dem Leitspruch "every cell has a sex" [2] und in den vergangenen Jahren dann auch global immer mehr zunehmend auf die erforderliche Berücksichtigung des Geschlechtes als relevante Variable hingewiesen [3]. Zwischenzeitlich wurden auch in Deutschland Kompetenzzentren zur geschlechtersensiblen Medizin initiiert, wie an der Berliner Charité oder durch einem Zusammenschluss von 8 medizinischen Fakultäten in Nordrhein-Westfalen, und es ist zeitnah beispielsweise eine Aufnahme in den Nationalen Kompetenzbasierten Lernzielkatalog Medizin (NKLM) geplant. ...
... Historically, biomedical research has been biased against female and non-human female mammals. Justifications include the assumption that findings derived from male subjects are universally applicable or fearing that hormonal variations in females might add complexity to study designs and interpretation of results [2]. However, emerging studies have shed light on distinctive sleep patterns in males and females, including sleep quality, duration, latency, and architecture [3,4]. ...
... With the emergence of sex or gender-specific medicine, recognizing differences in the diagnosis and treatment of diseases between males and females, gender has been considered a crucial factor in the pathogenesis, disease progression, and prognosis of various conditions [2,3]. Sex means biological differences characterizing males and females, while gender reflects sex-related social roles with which an individual identifies, and that presumably reflect learned femininity or masculinity [4]. It has been observed that IBS is predominantly diagnosed in women, with ratios ranging from 2:1 to 4:1, depending on the clinical setting, especially in the Western world [5]. ...
Background
Evidences of comparison of sex difference in Chinese irritable bowel syndrome (IBS) patients were few. We aim to compare gender difference in the biopsychosocial characteristics of Chinese patients of IBS predominant with diarrhea (IBS-D).
Methods
IBS-D patients meeting Rome III criteria were enrolled. We administered IBS symptom questionnaires, evaluation of psychological status (HAMD and HAMA scales) and IBS quality of life (IBS-QOL), dietary habits, healthcare seeking behaviors, and compared biopsychosocial characteristics between male and female patients.
Results
Four hundred and ninety patients were enrolled including 299 males and 191 females. More female patients reported abdominal pain associated with defecation (84.3% vs. 74.9%, P = 0.014) while males reported more abdominal discomfort (39.8% vs. 26.7%, P = 0.003). Females had higher IBS symptom score (9.7 ± 1.7 vs. 9.4 ± 1.4, P = 0.025) and more of females had severe abdominal pain/discomfort (17.8% vs. 12.4%, P = 0.013) while there were no significant differences of other bowel symptoms. Females reported higher incidence of comorbid anxiety state (64.9% vs. 52.8%, P = 0.008) and depression state (35.6% vs. 19.7%, P < 0.001) than males. Female patients also had lower IBS-QOL score (70.2 ± 20.4 vs. 75.1 ± 16.8, P = 0.028) and more frequent consultations, as well as less response for dietary modification than males.
Conclusions
Chinese female patients with IBS-D had more prominent psychosocial disorders compared to male patients and their abdominal symptoms had minor differences.
... Yet, ASD does affect females. Females of many species have historically been excluded from research studies for a variety of reasons, including sex discrimination, concerns about hormonal variation and reproductive health, and budgetary constraints [22,23]. However, exclusion of females from research studies can jeopardize identification of disease mechanisms and lead to sex-specific health disparities [24]. ...
Background
Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD.
Methods
Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models.
Results
Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found.
Limitations
This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores.
Conclusions
Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD.
... Sex refers to biological features such as chromosomes, physiological processes, and organs (including and beyond reproductive ability). 1 Gender, on the other hand, describes the characteristics of our socially constructed roles, behaviors, and identity. 2 Most treatment decisions are based on decades-long research using predominately male cells, animals, and individuals, 3 which is problematic given the growing body of data indicating sex differences in various diseases (especially pertaining to prevalence, symptoms, diagnosis, and prognosis). ...
Background
Although male and female cancer patients are distinct in many ways, there is a limited understanding in the differences between male and female biology and differing pharmacokinetic responses to cancer drugs. In fact, sex and gender are currently not considered in most treatment decisions in the fields of oncology and hematology. The lack of knowledge about potential sex differences in both disciplines may lead to differences in treatment efficacy, toxicity, and the overall survival (OS) of patients.
Aim
To evaluate their awareness about sex and gender in clinical practice we surveyed Swiss hematologists and oncologists from September to November 2022.
Methods
We collected data about the clinical knowledge, experimental research, palliative care, quality of life, as well as the participant perception of the importance of sex and gender. We identified 767 eligible clinicians, of whom 150 completed the survey (20% response rate).
Results
While most participants agreed that sex and gender were relevant when treating patients, it became clear that fewer participants knew about sex and gender differences in treatment toxicity and survival, which in turn would affect the treatment of their patients. Most participants agreed that this topic should be integrated into continuing education and research.
Conclusion
Our findings indicate the need for more awareness and training on sex and gender in cancer research and clinical care among oncologists and hematologists. Ideally, by better educating medical students and health professionals, a demand is created for improving research policies, publications and therefore patient care.
... Institute of Medicine (IOM) menyatakan bahwa perbedaan jenis kelamin adalah variabel fundamental penting yang harus dipertimbangkan saat merancang dan menganalisis penelitian dasar dan klinis. Selain dari perbedaan yang jelas terkait dengan organ khusus jenis kelamin dan peristiwa reproduksi, xenobiotik dapat berinteraksi secara berbeda dengan hormon seks pria dan wanita serta reseptornya (Wizemann & Pardue, 2001 Akuarium yang akan digunakan sebelumnya dicuci bersih kemudian dikeringkan selama 1 hari. Selanjutnya akuarium diisi dengan air sebanyak 10 liter kemudian diaerasi selama 1 hari untuk suplai O2. ...
Chlorpyrifos is one of the most widely used organophosphate insecticides used to control pests on plants. The use of insecticides will produce residues in the soil and on plants and can be carried by rain flows to water bodies. This can pollute aquatic ecosystems and could negatively affected the growth of aquatic biota like Oryzias celebensis. This study aimed to determine the susceptibility of male and female medaka celebes (Oryzias celebensis) to chlorpyrifos insecticide. In this study, five fish medaka celebes were put in each jar in one jar for male medaka fish and female medaka fish with five replications. The parameters measured were survival rate, oxygen consumption rate between male and female of O. celebensis, temperature and pH. Statistically the survival rate of male and female medaka fish showed no statistically significant difference (P>0.05). Likewise, there was no difference between the oxygen consumption levels of male and female medaka fish before and after exposure to chlorpyrifos insecticide (P>0.05). This study concluded that there was no difference in susceptibility to chlorpyrifos insecticides between male and female medaka fish.
... In recognition of sex-based biological differences, the Institute of Medicine (IOM) published a report in 2001 concluding that sex is a fundamental variable that should be considered at all levels of basic and clinical research [32]. Nevertheless, until 2005, sex was typically used as a confounder in neurotoxicology studies; few studies examined differential effects by sex. ...
Background
Early life exposure to lead, mercury, polychlorinated biphenyls (PCBs), polybromide diphenyl ethers (PBDEs), organophosphate pesticides (OPPs), and phthalates have been associated with lowered IQ in children. In some studies, these neurotoxicants impact males and females differently. We aimed to examine the sex-specific effects of exposure to developmental neurotoxicants on intelligence (IQ) in a systematic review and meta-analysis.
Method
We screened abstracts published in PsychINFO and PubMed before December 31st, 2021, for empirical studies of six neurotoxicants (lead, mercury, PCBs, PBDEs, OPPs, and phthalates) that (1) used an individualized biomarker; (2) measured exposure during the prenatal period or before age six; and (3) provided effect estimates on general, nonverbal, and/or verbal IQ by sex. We assessed each study for risk of bias and evaluated the certainty of the evidence using Navigation Guide. We performed separate random effect meta-analyses by sex and timing of exposure with subgroup analyses by neurotoxicant.
Results
Fifty-one studies were included in the systematic review and 20 in the meta-analysis. Prenatal exposure to developmental neurotoxicants was associated with decreased general and nonverbal IQ in males, especially for lead. No significant effects were found for verbal IQ, or postnatal lead exposure and general IQ. Due to the limited number of studies, we were unable to analyze postnatal effects of any of the other neurotoxicants.
Conclusion
During fetal development, males may be more vulnerable than females to general and nonverbal intellectual deficits from neurotoxic exposures, especially from lead. More research is needed to examine the nuanced sex-specific effects found for postnatal exposure to toxic chemicals.
... As women have historically been underrepresented in clinical studies and trials, 7 -9 further evidence is required to fully understand women's diseases or conditions throughout their life course. Globally, research for women's health had primarily focused on the anatomical and biological differences between men and women, 10 and yielded significant progress in the treatment of breast cancer, cardiovascular disease, and cervical cancer. 11 The recent national strategies for women's health research now aim to encompass the diverse health needs of women, along with evidence-based disease prevention and treatment tailored to women's specific needs. ...
Background:
With the epidemiological transition, sociodemographic changes and differential lifetime experiences of women, women's health research improves knowledge of diverse health issues and the impact of policies. To explore the initiatives of women's health research in Korea, the present study examined the trends and topics of research on women's health funded by the government.
Methods:
We searched all research projects on women's health funded by the government between 2012 and 2020 in Korea using the National Science & Technology Information Service database. We reviewed all the titles and abstract of the projects and examined the research trends by year. Content analysis was performed using both deductive and inductive approaches. Text network analysis and visualization by topic were conducted for keywords with a minimum of 10 occurrences in the title and abstract.
Results:
Total number and funding amount of research projects on women's health in 2020 increased by 2.4 and 2.2 times over 2012 levels, respectively. The Ministry of Health and Welfare and the Ministry of Food and Drug Safety funded 20.9% of all projects. The majority of the topics (59.8%) addressed breast and gynecological cancers. Those on sexual and reproductive health accounted for 16.7%, with steep growth in the number (6.1 times) and funding (11.1 times) over 2012 levels. The topic analysis presented a more complex keyword network in 2020 than in 2012; however, the keywords frequently used in 2020 were similar to those of 2012.
Conclusion:
Women's health research projects have been growing in number and funding, with limited diversity in topics. Diversifying the topics and focusing on issues beyond the breast and pregnancy would be needed to reflect the complete life course of women. Institutionalization of diverse communication channels with various interest groups for women's health would be needed to better understand women's health needs from a public health perspective.
... Over the last several decades, there has been increasing interest in the role of sex (a spectrum of biological and physiological differences traditionally characterized as male and female) and gender (socially constructed roles on a broad gender spectrum) in neurologic disease. 3,4 While understanding sex differences in neurologic disorders is pertinent to identify risk factors and targets for diagnostic and therapeutic measures, characterizing the role of gender often elucidates differences in the approach to and delivery of health care, [5][6][7] and the interplay of sex and gen-der is often seen in patient outcomes. 8 We sought to further characterize sex and gender differences influencing urinary dysfunction, assessment, and management in patients with MSA. 9 ...
Objective:
Multiple system atrophy (MSA) is characterized by urinary dysfunction, yet the influence of sex and gender on urinary symptoms and treatment is unclear. We sought to characterize sex and gender differences in the symptomatology, evaluation, and management of urinary dysfunction in patients with MSA.
Methods:
Patients with MSA evaluated at our institution were reviewed and stratified by sex.
Results:
While the prevalence of urinary symptoms was similar in male and female patients, incontinence was more common in females. Despite this, males and females underwent postvoid residual (PVR) measurement at similar rates. While catheterization rates were similar when PVR was measured, males were more than twice as likely to be catheterized than females in the absence of PVR measurement.
Conclusion:
Urinary symptoms are common in MSA, but their presentation differs between males and females. The difference in catheterization rates may be driven by a gender disparity in referrals for PVR, which can guide treatment.
... As early as November 1999, the Institute of Medicine (now the US National Academy of Medicine) formed a Committee on Understanding the Biology of Sex and Gender Differences and produced a report of their findings entitled Exploring the Biological Contributions to Human Health: Does Sex Matter? In their report, the committee pieced together the current, at the time, understanding of sex and gender in human health and made recommendations for the biomedical research community to consider SABV (19). In 2016, the US National Institutes of Health (NIH) introduced an SABV mandate as part of a broader initiative to improve the rigor and reproducibility of research funded by the NIH (20). ...
Although sex differences have been noted in cellular function and behavior, therapy efficacy, and disease incidence and outcomes, the adoption of sex as a biological variable in tissue engineering and regenerative medicine remains limited. Furthering the development of personalized, precision medicine requires considering biological sex at the bench and in the clinic. This review provides the basis for considering biological sex when designing tissue-engineered constructs and regenerative therapies by contextualizing sex as a biological variable within the tissue engineering triad of cells, matrices, and signals. To achieve equity in biological sex within medicine requires a cultural shift in science and engineering research, with active engagement by researchers, clinicians, companies, policymakers, and funding agencies.
Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 25 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... In preclinical research, "sex" is almost always the correct term to be used in the study of nonhuman animals [12]. The incorrect use of these terms is widespread, which is one contributing factor to these variables remaining relatively unexplored and misunderstood [13,14]. ...
Background
The importance of investigating sex- and gender-dependent differences has been recently emphasized by major funding agencies. Notably, the influence of biological sex on clinical outcomes in sepsis is unclear, and observational studies suffer from the effect of confounding factors. The controlled experimental environment afforded by preclinical studies allows for clarification and mechanistic evaluation of sex-dependent differences. We propose a systematic review to assess the impact of biological sex on baseline responses to disease induction as well as treatment responses in animal models of sepsis. Given the lack of guidance surrounding sex-based analyses in preclinical systematic reviews, careful consideration of various factors is needed to understand how best to conduct analyses and communicate findings.
Methods
MEDLINE and Embase will be searched (2011-present) to identify preclinical studies of sepsis in which any intervention was administered and sex-stratified data reported. The primary outcome will be mortality. Secondary outcomes will include organ dysfunction, bacterial load, and IL-6 levels. Study selection will be conducted independently and in duplicate by two reviewers. Data extraction will be conducted by one reviewer and audited by a second independent reviewer. Data extracted from included studies will be pooled, and meta-analysis will be conducted using random effects modeling. Primary analyses will be stratified by animal age and will assess the impact of sex at the following time points: pre-intervention, in response to treatment, and post-intervention. Risk of bias will be assessed using the SYRCLE’s risk-of-bias tool. Illustrative examples of potential methods to analyze sex-based differences are provided in this protocol.
Discussion
Our systematic review will summarize the current state of knowledge on sex-dependent differences in sepsis. This will identify current knowledge gaps that future studies can address. Finally, this review will provide a framework for sex-based analysis in future preclinical systematic reviews.
Systematic review registration
PROSPERO CRD42022367726.
... (Halberstam, 2017, p. 1) In this quote, when Halberstam refers to his "sex," not "gender," his meaning is not clear. Gender, as distinct from "sex," was only accepted academically in 2001 by the Institute of Medicine (Pardue and Wizemann, 2001)-at which time gender was defined as a self-understanding informed by social, cultural, and personal experience, as opposed to the biological classifier of "sex," assigned by reproductive organs, chromosomes, endogenous hormone production, and anatomy (Fausto-Sterling, 2012). Within this framework, both sex (Fausto-Sterling, 2012; R. E. Jones and Lopez, 2013) and gender (Fausto-Sterling, 2012) are multifaceted and nonbinary constructs. ...
Coming out as trans involves the melancholic, ambivalent loss of intentionally forsaken objects and illusions. Creating replacement fantasies for one’s gender expression requires navigating tensions between trying to visualize one’s authentic internal truth in the mirror (self-recognition) and seeking the affirmation and safety associated with external recognition, often referred to as passing. Ascribing to hegemonic binary gender norms can increase one’s legibility, but may impair self-recognition and one’s ability to form intimate connections with others, due to erasure of the authentic self. This can be particularly salient for nonbinary individuals, for whom passing necessitates choosing a least harmful form of misrecognition. I explored these themes in ethnographic interviews with 28 transgender, nonbinary, and/or gender-expansive individuals about their faces. Participants (binary and nonbinary) overwhelmingly fantasized about having facial features more stereotypically incongruent with their assigned-gender-at-birth (e.g., assigned-female-at-birth seeking angular jaw and cheekbones). They found the presence of such elements in their faces affirming or imagined a lack thereof to promote misrecognition. Paradoxically, these same persons were dissatisfied when such hypermasculinity or hyperfemininity was projected onto their faces by digital filters, due to loss of self-recognition.
... El término sexo hace referencia a la característica biológica, mientras que género está vinculado con preferencias, roles y conductas. En este sentido, según The Institute of Medicine (IOM), el sexo -determinado por los cromosomas XX o XY-es una variable biológica importante que debe ser considerada en las investigaciones y en los análisis que de ellas se derivan (Wizemann & Pardue, 2001). Además, aunque la literatura científica indica que existen multitud de similitudes entre sexos (Cosgrove et al., 2007), los estudios revelan también diferencias estructurales y funcionales a nivel cerebral (Choleris et al., 2018;Kurth et al., 2018;Luders et al., 2009;Ramos-Loyo et al., 2022;Ritchie et al., 2018;Ruigrok et al., 2014;Kanaan et al., 2014) y exponen la presencia de ciertos patrones de actividad neuronal característicos según el sexo, como respuesta a los mismos estímulos (Gegenhuber & Tollkuhn, 2020). ...
El entrenamiento musical reiterado puede modificar el cerebro tanto anatómicamente como en su función, pero existen una serie de variables que condicionan la neuroplasticidad. Este texto realiza una revisión actualizada sobre ellas, revisitándolas incluyendo las últimas investigaciones en el campo de la neurociencia de la música. Entre las variables de interés, se encuentran las diferencias individuales, el sexo, la lateralidad manual, la habilidad de oído absoluto, el instrumento que se interpreta, el tipo de formación musical que recibe el intérprete, las particularidades del entrenamiento –como la intensidad del mismo o la edad de inicio, por ejemplo–, además de otros factores ambientales y genéticos.
Background Equality, diversity and inclusion (EDI) has gained discursive momentum across multiple arenas, including in maternal health research. As a preliminary exploration for future discussion and development, we undertook a scoping review to identify the types, frequency, and extent of EDI characteristics that were measured and reported in randomised controlled trials (RCTs) of intrapartum interventions specifically. Methods Joanna Briggs Institute methodological guidance for scoping reviews guided the conduct of the review. The population were women of any parity and risk category who were enrolled in intrapartum RCTs in any birth setting or geographical location. The concept was measured and reported EDI characteristics. CINAHL, MEDLINE, PsycINFO, EMBASE, and CENTRAL were searched from January 2019 to March 2024. Data were extracted using a pre-designed form. The findings were summarised and narratively reported supported by illustrative tables and graphs. Results Two-hundred and forty-seven RCTs from 49 countries were included. Eleven EDI characteristics were measured or reported in at least one RCT, although frequency varied. Religion, for example, featured in three RCTs only, whereas Age featured in 222 RCTs. How the EDI characteristics featured also varied. Race/Ethnicity, for example, was described in 21 different ways in 25 RCTs. Similarly, Education was reported in 62 different ways across 96 RCTs. Ninety RCTs limited inclusion to nulliparous participants only, six RCTs required participants to have a minimum educational level, 127 RCTs had inclusion age cut-offs although 23 different variations of this were noted and 15 RCTs excluded participants on the grounds of disability. Conclusions This scoping review highlights EDI characteristic measurement and reporting deficits in intrapartum RCTs. There is a critical need for improvements in designing, conducting, and reporting RCTs to incorporate EDI. By adopting more extensive EDI practices a greater understanding of healthcare treatments and innovations leading to enhanced maternal health equity could be achieved.
In this article definitions of and concepts behind sex/gender-sensitive medicine (SGSM) are introduced. We evaluate why sex/gender-sensitive research is essential and how it can be sustainably implemented and nurtured to build a basis for sex/gender-sensitive clinical care. Further, statistical and clinical realities of disabled patients and patients of color are depicted, to illustrate intersectional discrimination in medical care. Practical tools are shared to guide the reader into implementing actionable change within their own clinical practice to contribute to a less discriminating experience for vulnerable populations.
Biological and sociocultural factors related to sex and gender interact to influence noncommunicable diseases. However, as individuals enter adulthood and approach old age, the influence of gender, which is connected to social and cultural factors, becomes stronger than that of sex. These sex and gender factors intermingle with each other, resulting in the final manifestation of disease. The representative diseases are irritable bowel syndrome (IBS), gout, and alcohol-related diseases. For individuals who have the same symptoms of IBS, women experience a more severe deterioration in quality of life than men due to differences in social norms and sexual identity. For example, abdominal bloating is typically perceived by men simply as physical discomfort, but women experience further psychological stress because abdominal bloating makes them appear to have gained weight. Next example is gout. In terms of sex, females are protected against gout in the premenopausal period due to uricosurics effect of estrogen, and therefore males outnumber females in all age groups, more in the younger than older age groups by a ratio of 10:1 to 5:1. In terms of gender, women are less likely to take allopurinol and less likely to undergo joint aspirations for crystal analysis to establish diagnosis than men. Another example is alcohol-related diseases. Due to biological differences in alcohol metabolism, women are more intensely affected by alcohol than men. In addition, physical diseases related to alcohol consumption manifest earlier in women and progress more rapidly. In terms of gender, high-risk alcohol consumption is increasing in women in their 20s and 30s because women’s increasing participation in the workforce increases opportunities to alcohol. Furthermore, alcohol problems in women often stem from attempts to relieve stress from work and family duties. Both the general public and medical professionals, such as doctors and nurses, should understand sex/gender differences in reasons for drinking alcohol and the multifaceted effects of alcohol on the body. In addition, medical staffs need to understand the effects of gender on IBS, a chronic and recurrent disease, and the concept of women who are recently diagnosed as gout and the attitudes to the diagnostic approach and treatments of gout.
Wild zebrafish (Danio rerio) have a ZZ/ZW chromosomal sex determination system with the major sex locus on the right arm of chromosome-4 (Chr4R) near the largest heterochromatic block in the genome, suggesting that Chr4R transcriptomics might differ from the rest of the genome. To test this hypothesis, we conducted an RNA-seq analysis of adult ZW ovaries and ZZ testes in the Nadia strain and identified four regions of Chr4 with different gene expression profiles. Unique in the genome, protein-coding genes in a 41.7 Mb section (Region-2) were expressed in testis but silent in ovary. The AB lab strain, which lacks sex chromosomes, verified this result, showing that testis-biased gene expression in Region-2 depends on gonad biology, not on sex-determining mechanism. RNA-seq analyses in female and male brain and liver validated reduced transcripts from Region-2 in somatic cells, but without sex-specificity. Region-2 corresponds to the heterochromatic portion of Chr4R and its content of genes and repetitive elements distinguishes it from the rest of the genome. Region-2 lacks protein-coding genes with human orthologs; has zinc finger genes expressed early in zygotic genome activation; has maternal 5S rRNA genes, maternal spliceosome genes, a concentration of tRNA genes, and a distinct set of repetitive elements. The colocalization of 1) genes silenced in ovaries but not in testes that are 2) expressed in embryos briefly at the onset of zygotic genome activation; 3) maternal-specific genes for translation machinery; 4) maternal-specific spliceosome components; and 4) adjacent genes encoding miR-430, which mediates maternal transcript degradation, suggest that this is a Maternal-to-Zygotic-Transition Gene Regulatory Block.
Until now, research has been performed mainly in men, with a low recruitment of women; consequentially, biological, physiological, and physio-pathological mechanisms are less understood in women. Obviously, without data obtained on women, it is impossible to apply the results of research appropriately to women. This issue also applies to medical devices (MDs), and numerous problems linked to scarce pre-market research and clinical trials on MDs were evidenced after their introduction to the market. Globally, some MDs are less efficient in women than in men and sometimes MDs are less safe for women than men, although recently there has been a small but significant decrease in the sex and gender gap. As an example, cardiac resynchronization defibrillators seem to produce more beneficial effects in women than in men. It is also important to remember that MDs can impact the health of healthcare providers and this could occur in a sex- and gender-dependent manner. Recently, MDs’ complexity is rising, and to ensure their appropriate use they must have a sex–gender-sensitive approach. Unfortunately, the majority of physicians, healthcare providers, and developers of MDs still believe that the human population is only constituted by men. Therefore, to overcome the gender gap, a real collaboration between the inventors of MDs, health researchers, and health providers should be established to test MDs in female and male tissues, animals, and women.
Studying proteins associated with sex chromosomes can provide insights into sex-specific proteins. Membrane proteins accessible through the cell surface may serve as excellent targets for diagnostic, therapeutic, or even technological purposes, such as sperm sexing technologies. In this context, proteins encoded by sex chromosomes have the potential to become targets for X- or Y-chromosome-bearing spermatozoa. Due to the limited availability of proteomic studies on rabbit spermatozoa and poorly annotated databases for rabbits compared to humans, a bioinformatic analysis of the available rabbit X chromosome proteome (RX), as well as the human X (HX) and Y (HY) chromosomes proteome, was conducted to identify potential targets that could be accessible from the cell surface and predict which of the potential targets identified in humans might also exist in rabbits. We identified 100, 211, and 3 proteins associated with the plasma membrane or cell surface for RX, HX, and HY, respectively, of which 61, 132, and 3 proteins exhibit potential as targets as they were predicted to be accessible from the cell surface. Cross-referencing the potential HX targets with the rabbit proteome revealed an additional 60 proteins with the potential to be RX targets, resulting in a total of 121 potential RX targets. In addition, at least 53 possible common HX and RX targets have been previously identified in human spermatozoa, emphasizing their potential as targets of X-chromosome-bearing spermatozoa. Further proteomic studies on rabbit sperm will be essential to identify and validate the usefulness of these proteins for application in rabbit sperm sorting techniques as targets of X-chromosome-bearing spermatozoa.
Wild zebrafish (Danio rerio) have a ZZ/ZW chromosomal sex determination system with the major sex locus on the right arm of chromosome-4 (Chr4R) near the largest heterochromatic block in the genome, suggesting the hypothesis that the Chr4R transcriptome might be different from the rest of the genome. We conducted an RNA-seq analysis of adult ZW ovaries and ZZ testes and identified four regions of Chr4 with different gene expression profiles. Unique in the genome, protein-coding genes in a 41.7 Mb section (Region-2) were expressed in testis but silent in ovary. The AB lab strain, which lacks sex chromosomes, verified this result, showing that testis-biased gene expression in Region-2 depends on gonad biology, not on sex-determining mechanism. RNA-seq analyses in female and male brain and liver validated few transcripts from Region-2 in somatic cells, but without sex-specificity. Region-2 corresponds to the heterochromatic portion of Chr4R and its content of genes and repetitive elements distinguishes it from the rest of the genome. In Region-2, protein-coding genes lack human orthologs; it has zinc finger genes expressed early in zygotic genome activation; it has maternal 5S rRNA genes, maternal spliceosome genes, a concentration of tRNA genes, and an distinct set of repetitive elements. The colocalization of 1) genes silenced in ovaries but not in testes that are 2) expressed in embryos briefly at the onset of zygotic genome activation; 3) maternal-specific genes for translation machinery; 4) maternal-specific spliceosome components; and 4) adjacent genes encoding miR-430, which mediates maternal transcript degradation, suggest that this is a Maternal-to-Zygotic-Transition Gene Regulatory Block.
Purpose:
The Sex Differences in Radiation Research workshop addressed the role of sex as a confounder in radiation research and its implication in real-world radiological and nuclear applications.
Methods:
In April 2022, HHS-wide partners from the Radiation and Nuclear Countermeasures Program, the Office of Research on Women's Health National Institutes of Health Office of Women's Health, U.S. Food and Drug Administration, and the Radiological and Nuclear Countermeasures Branch at the Biomedical Advanced Research and Development Authority conducted a workshop to address the scientific implication and knowledge gaps in understanding sex in basic and translational research. The goals of this workshop were to examine sex differences in 1. Radiation animal models and understand how these may affect radiation medical countermeasure development; 2. Biodosimetry and/or biomarkers used to assess acute radiation syndrome, delayed effects of acute radiation exposure, and/or predict major organ morbidities; 3. medical research that lacks representation from both sexes. In addition, regulatory policies that influence inclusion of women in research, and the gaps that exist in drug development and device clearance were discussed. Finally, real-world sex differences in human health scenarios were also considered.
Results:
This report provides an overview of the two-day workshop, and open discussion among academic investigators, industry researchers, and U.S. government representatives.
Conclusions:
This meeting highlighted that current study designs lack the power to determine statistical significance based on sex, and much is unknown about the underlying factors that contribute to these differences. Investigators should accommodate both sexes in all stages of research to ensure that the outcome is robust, reproducible, and accurate, and will benefit public health.
The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various tissues. Recent research has suggested that specific dietary components may influence the function of the intestinal barrier, potentially offering a means to prevent or mitigate inflammatory disorders. However, the precise mechanism underlying these effects remains unclear. Bovine colostrum (BC), the first milk from cows after calving, is a natural source of nutrients with immunomodulatory, anti-inflammatory, and gut-barrier fortifying properties. This novel study sought to investigate the transcriptome in BC-treated Zonulin transgenic mice (Ztm), characterized by dysbiotic microbiota, intestinal hyperpermeability, and mild hyperactivity, applying RNA sequencing. Seventy-five tissue samples from the duodenum, colon, and brain of Ztm and wild-type (WT) mice were dissected, processed, and RNA sequenced. The expression profiles were analyzed and integrated to identify differentially expressed genes (DEGs) and differentially expressed transcripts (DETs). These were then further examined using bioinformatics tools. RNA-seq analysis identified 1298 DEGs and 20,952 DETs in the paired (Ztm treatment vs. Ztm control) and reference (WT controls) groups. Of these, 733 DEGs and 10,476 DETs were upregulated, while 565 DEGs and 6097 DETs were downregulated. BC-treated Ztm female mice showed significant upregulation of cingulin (Cgn) and claudin 12 (Cldn12) duodenum and protein interactions, as well as molecular pathways and interactions pertaining to tight junctions, while BC-treated Ztm males displayed an upregulation of transcripts like occludin (Ocln) and Rho/Rac guanine nucleotide exchange factor 2 (Arhgf2) and cellular structures and interfaces, protein–protein interactions, and organization and response mechanisms. This comprehensive analysis reveals the influence of BC treatment on tight junctions (TJs) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway gene expressions. The present study is the first to analyze intestinal and brain samples from BC-treated Ztm mice applying high-throughput RNA sequencing. This study revealed molecular interaction in intestinal barrier function and identified hub genes and their functional pathways and biological processes in response to BC treatment in Ztm mice. Further research is needed to validate these findings and explore their implications for dietary interventions aimed at improving intestinal barrier integrity and function. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).
In vitro models play a crucial role in advancing our understanding of biological processes, disease mechanisms, and developing screening platforms for drug discovery. Kidneys play an instrumental role in transport and elimination of drugs and toxins. However, despite the well-established patient-to-patient differences in kidney function and disease manifestation, progression and prognostic, few studies take this variability into consideration. In particular, the discrepancies between female and male biology warrants a better representation within kidney in vitro models. The omission of sex as a biological variable poses the significant risk of overlooking sex-specific mechanisms in health and disease and potential differences in drug efficacy and toxicity between males and females. This review aims to highlight the importance of incorporating sex dimorphism in kidney in vitro models by examining the sexual characteristics in the context of the current state-of-the-art. Furthermore, this review underscores opportunities for improving kidney models by incorporating sex-specific traits. Ultimately, this roadmap to incorporating sex-dimorphism in kidney in vitro models will facilitate the creation of better models for studying sex-specific mechanisms in the kidney and their impact on drug efficacy and safety.
To characterize the immunogenicity of mRNA-1273 (Moderna, Cambridge, MA, USA) vaccine in HIV-positive hemophilic patients during the third COVID-19 wave in Italy and to investigate biomarkers of coagulation and endothelial perturbation before and after complete vaccination schedule, twenty-three consecutive adult HIV-positive patients with hemophilia were included. Blood was collected before and two weeks after vaccination. We measured anti-SARS-CoV-2 spike protein antibodies to assess immunogenicity; circulating biomarkers of coagulation (protein C and D-dimer), endothelial perturbation (von Willebrand factor (VWF)) and anti-Platelet Factor 4 (PF4) antibodies were analyzed. Flow-based analysis of thrombus formation was performed in nine patients using a flow-chamber device. Two weeks after completing the vaccination schedule, all patients had anti-spike antibodies values consistent with an effective immunization. Mean (±standard deviation) basal values of protein C and VWF (106 ± 21% and 171 ± 45%, respectively) were not significantly different from data obtained two weeks after the second dose (103 ± 20%, 162 ± 43%, respectively). D-dimer median values (interquartile range) were not significantly different at baseline (442 (603–142) ng/mL) and after the second dose (477 (654–262) ng/mL). Anti-PF4 antibodies were detected in three patients with no associated clinical manifestations. No significant differences were found in flow-based analysis of thrombus formation. Our data demonstrate that in HIV-positive patients with hemophilia, SARS-CoV-2 vaccination is effective and safe, with no effects on coagulation and endothelial perturbation.
Sex and gender play a pivotal role in health and disease. Differences can be identified in symptoms, biomarkers, lifetime experiences of diseases, incidence, prevalence, therapeutic options, health-related behavior, and resiliency. However, awareness of sex and gender differences in medicine is still limited. Systematic implementation of sex and gender-sensitive research is not yet the norm, resulting in gaps in evidence especially in the diagnosis and treatment of diseases in women. For decades research has predominantly included male persons and animals, leading to a lack of information about symptoms in female individuals or the classification of their symptoms as “atypical”. Currently, the inclusion of female participants in clinical marketing access trials is mandatory. However, this does not automatically translate into sex-disaggregated analyses potentially limiting the discovery of sex-specific targeted therapeutic schemes. Consistent consideration of sex and gender in planning, conducting, analyzing, and dissemination of pharmacological research projects is an important prerequisite for closing the gender data gap. Targeted implementation strategies might help to include sex and gender aspects in different parts of the health system and thereby support the improvement of health care for all patients. Health economic aspects could be a further drive for the implementation of sex- and gender-sensitive medicine.
The current chapter focuses on the role of sex and gender in biomedical research and, consequently, their potential role in pharmacology. We will explore the commonly used terminology in the field, the historical development of sex and gender-sensitive medicine (SGSM), the relevance of sex and gender to research and clinical practice and conclude with an outlook on future developments in the field.
Pain is a highly personal experience. Pain is often considered to be a purely neurologic phenomenon, but in actuality, it is a combination of both sensory and emotional experiences. This has sometimes been translated clinically toward a more mechanistic approach to the assessment and treatment of pain instead of one that does not discount pain mechanisms, but also is more inclusive of the need for humanism – considering the individual. In today’s medical environment, more than ever before there is a significant amount of attention being paid to educating clinicians to better understand that several physiological, neurophysiological, and psychosocial factors can significantly impact responses to pain. The composition of these factors will be unique to that individual’s life narrative, context, sex, and prior life experiences. Thus, the concept that a templated approach to pain assessment and pharmacotherapeutic treatment planning should not be expected to provide optimal patient satisfaction and treatment outcomes in the majority. The hypotheses that there may be sex-based differences in the pain experience in a variety of ways including pain sensitivity, tolerance to pain, threshold at which something becomes painful, and the effectiveness of endogenous pain modulation systems are not new and have been well represented in the literature. This chapter reviews important key findings in the scientific literature with respect to sex-based differences in pain and pain responses to experimentally induced painful stimuli, pain experienced in commonly occurring painful medical conditions, and variations in responses to pain treatments. Possible explanations to account for observed differences or similarities will also be discussed.KeywordsAnalgesiaBiasDifferenceDisparitiesNociceptionPainPain researchSexSex-based differencesSex-specificSpecial patient populationStereotype
Background:
There is significant debate regarding the existence of sex-related differences in the presentation, treatment, and outcomes of men versus women affected by abdominal aortic aneurysm (AAA). The purpose of this study is to compare endovascular aneurysm repair (EVAR) of infrarenal AAAs with the current sex-neutral 5.0-5.5 cm-diameter threshold for intervention between the two sexes.
Methods:
Retrospective review of consecutive cases from a single teaching institution over a period of five years of patients who had undergone elective EVAR for AAAs between 5.0 and 5.5 cm in diameter. Outcomes of interest were compared according to sex.
Results:
Ninety-four patients were included in the analysis, with a higher prevalence of men (53%). Females were older at the time of repair, 78 ± 5.1 years, versus 71.7 ± 7 years (p < 0.01), and had higher incidence of underlying comorbidities, namely, arrhythmia, chronic kidney disease, and previous carotid revascularization. Women had higher incidence of immediate systemic complications (p = 0.021), post-operative AMI (p = 0.001), arrhythmia (p = 0.006), pulmonary oedema (p < 0.001), and persistent renal dysfunction (p = 0.029). Multivariate analysis for post-operative factors associated to mortality and adjusted for sex confirmed that AMI (p = 0.015), arrhythmia (p = 0.049), pulmonary oedema (p = 0.015), persistent renal dysfunction (p < 0.001), cerebral ischemia (p < 0.001), arterial embolism of lower limbs (p < 0.001), and deep-vein thrombosis of lower limbs (p < 0.001) were associated to higher EVAR-related mortality; a higher incidence of post-operative AMI (p = 0.014), pulmonary edema (p = 0.034), and arterial embolism of lower limbs (p = 0.046) were associated to higher 30-days mortality. In females there was also a higher rate of suprarenal fixation (p = 0.026), insertion outside the instruction for use (p = 0.035), and a more hostile neck anatomy with different proximal aortic diameter (p < 0.001) and angle (p = 0.003).
Conclusions:
A similar threshold of size of AAA for elective surgery for both males and females might not be appropriate for surgical intervention, as females tend to have worse outcomes. Further population-based studies are needed to guide on sex-related differences and intervention on AAA.
Vivemos numa época em que já poucos mistérios persistem, mas talvez dois ainda suscitem o nosso fascínio e interesse em transcender as fronteiras do conhecimento que limitam a sua compreensão. Um é o macrocosmo dos corpos celestes do universo e do espaço infinitamente grande. O outro é o microscomo do nosso cérebro, contido na nossa cabeça, mas que também encerra galáxias de complexidade no intrincado funcionamento molecular das suas células e no pulsar elétrico dos seus neurónios. Este órgão que é o ator e autor de todos os nossos pensamentos, emoções, ações, sonhos e planos está tão perto, afinal todos temos um, mas tão longe do nosso completo entendimento. Por isso, o cérebro é o protagonista deste livro que nos convida e desafia para uma digressão conceptual que não tem ponto de partida, nem de chegada, antes constitui um percurso polissémico, que suscita mais questões do que respostas.
Traumatized patients are more likely to present to primary care and other health care services than to mental health care providers. The present chapter covers gender differences from exposure and response to traumatic events to development and treatment of trauma-related disorders. Gender affects the type of traumatic events to which men and women are exposed, how they respond, and the subsequent sequelae they suffer. For both men and women, psychological trauma is associated with extensive mental and somatic morbidity, including posttraumatic stress disorder (PTSD). Some symptoms are clearly linked to the traumatic event whereas others are not. These may substantially complicate the treatment of patients in primary care. If detected, trauma-related disorders can be treated with either pharmacotherapy or psychotherapy, though there may be gender differences in the outcomes associated with both approaches. The present chapter aims to raise awareness for the importance of trauma and gender in primary care so that healthcare providers may become better equipped to identify and treat traumatized patients, hopefully preventing traumatic sequelae from becoming chronic.
Gender equality issues never stop being discussed and always attract attention. This is driven by the many inequalities experienced by women from ancient times until now. Even though gender equality is increasingly being echoed, the position of women is always affected and biased by patriarchal culture. Often women are made second. Islam itself provides space for gender equality. This study aims to discuss Riffat Hassan's thoughts on realizing gender equality in the Islamic view. This study also uses a qualitative descriptive method with a narrative analysis approach. The data was collected by documenting various sources related to Hassan and her thoughts and was analyzed using interactive qualitative analysis. The results show that there are two approaches used by Riffat Hassan in interpreting the verses of the Koran: the ideal-normative and socio-historical approaches. In her view, the basis of a contested patriarchal culture is related to 1) God first created men, not women; women are believed to have been created from the ribs of men. Therefore, women are derivative and ontologically secondary; 2) women, not men, are the primary agents for human fall from heaven; and 3) women are not only created by men but also for men, so the existence of women is only a tool and has no fundamental meaning.
Lacrimal gland dysfunction causes dry eye disease (DED) due to decreased tear production. Aqueous-deficient DED is more prevalent in women, suggesting that sexual dimorphism of the human lacrimal gland could be a potential cause. Sex steroid hormones are a key factor in the development of sexual dimorphism. This study aimed to quantify estrogen receptor (ER) and androgen receptor (AR) expression in the human lacrimal gland and compare it between sexes. RNA was isolated from 35 human lacrimal gland tissue samples collected from 19 cornea donors. AR, ERα, and ERβ mRNA was identified in all samples, and their expression was quantified using qPCR. Immunohistochemical staining was performed on selected samples to evaluate protein expression of the receptors. ERα mRNA expression was significantly higher than the expression of AR and ERβ. No difference in sex steroid hormone (SSH) receptor mRNA expression was observed between sexes, and no correlation was observed with age. If ERα protein expression is found to be concordant with mRNA expression, it should be investigated further as a potential target for hormone therapy of DED. Further research is needed to elucidate the role of sex steroid hormone receptors in sex-related differences of lacrimal gland structure and disease.
The mechanisms that control blood pressure are multifaceted including the sympathetic nervous system and the renin-angiotensin system leading to vasoconstriction and sodium reabsorption that causes a shift in the pressure-natriuesis relationship to higher blood pressures. Sex steroids can affect these mechanisms either directly or indirectly, and the effects may be different depending on the sex of the individual. This review will discuss some of the major blood pressure-controlling mechanisms and how sex steroids may affect them and the need for future studies to better clarify the mechanisms responsible for sex and gender differences in blood pressure control. New mechanisms that are identified, along with what is already known, will provide better tools for treatment of hypertension in men and women of all ethnicities and decrease the risk of cardiovascular disease in the future.
Cette étude porte sur le français langue première et vise deux objectifs : comparer la conscience morphologique (CM) de bilingues et monolingues ; déterminer la contribution de la CM à la lecture et préciser si elle est modérée par le bilinguisme. La CM est mesurée par des tâches de complètement de phrases par une forme fléchie ou dérivée et d’extraction de la base, et la lecture par des tests standardisés (EVALEC et Alouette). Soixante-neuf bilingues français-portugais en 1 re , 3 e et 5 e année ont été comparées à 69 monolingues. Les résultats montrent systématiquement une supériorité bilingue en CM et une contribution de celle-ci à la lecture-fluence en 1 re année et à la lecture-précision aux niveaux suivants, pour les bilingues comme pour les monolingues. Ces résultats approfondissent la notion d’avantage bilingue et le rôle de la CM en lecture en particulier sur la précision en lecture.
What is evolutionary psychology? Cognition and behavior in the light of evolution
Evolutionary psychology aims to understand human cognitive organisation and functioning in the light of evolutionary theory. Despite its growing acceptance among scientists as a metatheory of the mind, evolutionary psychology has yet to find its place in the French scientific literature. This article aims to provide a general introductory framework to evolutionary psychology. We describe how natural selection shaped cognition and behavior, and what it entails for conceptualizing the human mind. We also explore how sexual selection acted as a key driver for the evolution of psychological differences between men and women. Finally, we address the most recurrent critics directed at evolutionary psychology.
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